自愈水凝胶
椎间盘
生物相容性
材料科学
药物输送
明胶
炎症
活性氧
肿瘤微环境
体内
药理学
化学
细胞生物学
癌症研究
医学
生物化学
解剖
纳米技术
免疫学
生物
高分子化学
生物技术
肿瘤细胞
冶金
作者
Lei Liu,Wantao Wang,Lin Huang,Yiwen Xian,Wenzheng Ma,Jinghao Fan,Yixi Li,Hongmei Liu,Zhaomin Zheng,Decheng Wu
出处
期刊:Biomaterials
[Elsevier]
日期:2024-04-01
卷期号:306: 122509-122509
被引量:2
标识
DOI:10.1016/j.biomaterials.2024.122509
摘要
Chronic local inflammation and resulting cellular dysfunction of nucleus pulposus (NP) cells are important pathogenic factors of intervertebral disc degeneration (IDD). Injectable pathological microenvironment-responsive hydrogels hold significant potential for treating IDD by adapting to dynamic microenvironment of IDD. Herein, we proposed an injectable gelatin-based hydrogel drug delivery system that could respond to the pathological microenvironment of IDD for controlled release of anti-inflammatory drug to promote degenerative NP repair. The hydrogel system was prepared by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with the naturally extracted anti-inflammatory drug epigallocatechin-3-gallate (EGCG) through dynamic boronic esters. The hydrogel exhibited excellent degradability, injectability, antioxidant properties, anti-inflammatory effects, and biocompatibility. It also displayed responsive-release of EGCG under high reactive oxygen species (ROS) levels and acidic conditions. The hydrogel demonstrated remarkable cytoprotective effects on NP cells in both hyperactive ROS environments and inflammatory cytokine-overexpressed environments in vitro. In vivo studies revealed that the hydrogel injected in situ could effectively ameliorate the intervertebral disc degeneration by maintaining the disc height and NP tissue structure in a rat IDD model. The hydrogel system exhibited excellent biocompatibility and responsive-release of diol-containing drugs in pathological microenvironments, indicating its potential application as a drug delivery platform.
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